Chemical sensors based on receptor-doped polymeric membranes were developed for over 60 analytes. They are routinely used worldwide in clinical chemistry for well over a billion measurements per year. Unfortunately, their lifetimes are limited by lipids and hydrophobic proteins that adsorb onto or are extracted into these membranes. This hinders their wider use, in particular for the long-term implantation into the human body. Perfluorocarbon matrixes have great promise to solve this problem of sensor lifetime because their low polarity limits the solubility of lipids and proteins. The extraordinarily low polarity of perfluorocarbons is illustrated by the following example: On the pi * scale of solvent polarity, water has a pi* value of 1, hexane defines 0, and perfluorooctane has the astounding value of-0.41. Indeed, it is well documented that lipids are poorly soluble in perfluorocarbons. Therefore, it is expected that nonpolar perfluorinated membrane matrixes will not lose their selectivies when exposed to biological fluids containing lipids and hydrophobic proteins. Moreover, nonpolar perfluorinated matrixes (i) will exhibit much higher selectivities than conventional receptor-doped sensor matrixes because lipophilic interferents are hardly solvated in perfluorinated phases, (ii) are chemically very inert, and (iii) were shown to promote cell growth on their surface to a much lesser extent than most polymers presently used for receptor-based sensors. Despite the attractiveness of perfluorinated phases, the current literature does not describe any receptorbased sensor with a nonpolar perfluorinated matrix. Neither receptors nor electrolyte salts that are soluble in perfluorocarbon phases were reported. This research will develop perfluorinated polymeric matrixes and fluorophilic ion exchanger sites required for the preparation of receptor-based sensors. Three representative fluorophilic receptors will be synthesized and used for the preparation of potentiometric sensors. The robustness of these sensors will be tested with pure solutions of individual lipids, blood serum and urine samples. In brief, specific goals include the development of (i) fluorophilic cations and anions suitable as ionic sites for potentiometric sensors, (ii) a fluorophilic electrolyte salt, (iii) perfluorinated polymers suitable as matrixes for potentiometric sensors, (iv) proton-, creatininium-, and chloride-selective sensors based on perfluorinated membranes for applications in biological samples, and (v) perfluorinated sensing membranes surface-modified with poly(ethylene glycol) for a further improvement of their biocompatibility. The introduction of perfluorinated sensor matrixes will enhance the selectivity, robustness and lifetime of chemical sensors for clinical chemistry. It will also permit other novel uses of receptor-based chemical sensors under harsh conditions, such as long-term environmental monitoring with sensor networks for the prediction of earthquakes and process control in the food industry and manufacturing.